S. C. Blacklow

Structural Requirements for Activity of Mind bomb1 in Notch Signaling

This study identifies the structural requirements of MIB1 for ubiquitin transfer in Notch signaling, showing that RING3 is essential for catalytic activity and dimerization.

Temporal Dynamics and Stoichiometry in Notch Signaling - from Notch Synaptic Complex Formation to NICD Nuclear Entry

This study tracks Notch and Delta interactions in real-time, showing 1:1 stoichiometry at synapses and NICD nuclear entry after 45 minutes, inhibited by signaling blockers.

Molecular Mechanism of PP2A/B55α Phosphatase Inhibition by IER5

This study determines the structure of PP2A/B55 inhibited by IER5-N50 and shows its role in suppressing pTau dephosphorylation and KRT1 expression.

A Spatiotemporal Map of Co-Receptor Signaling Networks Underlying B Cell Activation

This study maps B cell co-receptor signaling dynamics using proximity labeling and mass spectrometry, identifying new mediators of B cell activation and metabolic reprogramming.

Structural Basis for Selective Proteolysis of ADAM10 Substrates at Membrane-Proximal Sites

This study determines the cryo-EM structure of ADAM10-Tspan15 complex, revealing how Tspan15 relieves autoinhibition and positions the active site for membrane-proximal substrate cleavage.

Tethered agonist activated ADGRF1 structure reveals molecular preference for Gq signaling

The paper reports the cryo-EM structure of ADGRF1, revealing structural features that explain its preference for Gq signaling over Gs.

Heterogeneity of Tethered Agonist Signaling in Adhesion G Protein-Coupled Receptors

The paper profiles tethered agonist (TA) signaling in all 33 human aGPCRs using a platform across assays, revealing heterogeneous responses and aligning with AlphaFold2 predictions.

An affinity-matured DLL4 ligand for broad-spectrum activation and inhibition of Notch signaling

This study develops DeltaMAX, an affinity-matured DLL4 ligand that broadly activates or inhibits Notch signaling in human and murine systems.

Targeted degradation of the oncogenic phosphatase SHP2

This paper develops a SHP2 PROTAC that degrades SHP2 in leukemic cells, inhibits MAPK signaling, and suppresses cancer growth.

IER5, a DNA-damage response gene, is required for Notch-mediated induction of squamous cell differentiation

The paper identifies IER5 as a Notch-induced DNA-damage response gene required for squamous cell differentiation and shows its interaction with PP2A subunit PPP2R2A.

A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking

This study shows that CD81 controls CD19 trafficking to the cell surface through a dynamic interaction, with implications for B cell function and tetraspanin biology.

Molecular basis for feedback inhibition of Notch signaling by the Notch regulated ankyrin repeat protein NRARP

This study identifies the molecular mechanism by which NRARP inhibits Notch signaling by binding to the NTC complex and disrupting its function.

Development of a Covalent Inhibitor of Gut Bacterial Bile Salt Hydrolases

This study develops a covalent inhibitor of gut bacterial bile salt hydrolases, showing it reduces BSH activity and deconjugated bile acids in mice.

Time resolved quantitative phosphoproteomics reveals distinct patterns of SHP2 dependence in EGFR signaling

The paper uses time-resolved phosphoproteomics to analyze SHP2's role in EGFR signaling, identifying distinct phosphotyrosine response patterns upon SHP099 treatment.

A flow extension tethered particle motion assay for single-molecule proteolysis

This paper introduces a flow extension tethered particle motion assay to study single-molecule proteolysis, enabling accurate assessment of protease activity by excluding multiply-tethered beads.